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In 2002, Lydia Sohn helped blow the whistle on an esteemed Bell Labs physicist who falsified data in high-profile scientific publications. (courtesy the researcher)

A tiny chip developed by a UC Berkeley mechanical engineer is now being tested as a super-fast bioterrorism sensor for the battlefield. The same technology could eventually lead to a disposable disease detector that brings cheap, easy, and incredibly accurate blood tests out of the clinic and into the rural villages of developing nations. To build such a device though, professor Lydia Sohn looked to nature for inspiration. The result is a silicon chip laden with artificial nanopores that mimic the filtration system of human cells.

"My background is in solid state physics and nanotechnology," says Sohn, formerly a physics professor at Princeton University. "But six years ago, I realized that the electronics I was working on were so sensitive that the same concepts could be used for biological detection."

Currently, blood samples are screened for pathogens or diseases mostly through optical detection of antigens or antibodies. Antibodies are formed by the body in response to antigens-- molecules, often foreign, that the immune system recognizes as threats. For every antigen, there is an antibody that binds to it. In one common test, an enzyme is added to a sample that activates a visible colored dye in the presence of a particular antigen or antibody indicative of a particular disease. The problem is that this test requires laboratory equipment not suited for the battlefield or rural villages where even clean water may be a luxury.

On the other hand, Sohn's device--first developed in collaboration with former Princeton graduate student Omar Saleh--is entirely integrated on a single, inexpensive electronic chip. Because the biosensor is fabricated using processes similar to the way integrated circuits are manufactured, the devices can be produced in bulk at very low cost.

This scanning electron micrograph depicts a nanopore made from quartz. More recent prototypes are fabricated from rubber, an easier material to work with. (courtesy the researcher)

A cell's membrane is riddled with tiny pores, each engineered by evolution to allow a certain substance to pass through while blocking others. Molded out of silicon rubber, Sohn's artificial nanopore consists of a tiny channel just one micron in diameter and around seven microns long. (A human hair is 100 microns thick.) The pore is filled with a conducting fluid so that tiny electrodes on the chip underneath can measure the current across the channel. Small plastic particles of specific sizes, called colloids, flow through the channel. As a colloid moves through the pore, it displaces some of the conducting fluid and reduces the current by a predictable amount. Differently-sized colloids can be coated with specific antigens that correspond to four different diseases or pathogens.

"We then dunk the device into a solution of blood," Sohn says. "If a certain antibody is there, it will be bind to the specific colloid for that disease, increasing the size of the colloid by a few nanometers."

When a colloid with an antibody bound to it flows through the pore, more of the conducting fluid is displaced than if the colloid passed through by itself. The additional drop-off in current signals the presence of the antibody while the amount of the drop indicates which colloid of a particular size is in the pore and, subsequently, the precise pathogen in the blood.

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Sohn's laboratory recently shipped 100 of the prototype biosensors to the US Army's Edgewood Chemical Biological Center in Maryland where the technology will be further developed for potential military deployment. Meanwhile, Sohn hopes to expand the device's capabilities.

Employing traditional lithographic manufacturing enables arrays of nonpores to be built on a single silicon wafer, she says, much like a multitude of transistors are etched into a silicon chip. For example, a ten-by-ten array of pores, with each pore capable of detecting a minimum of four diseases, could result in a single sensor that can screen for four hundred diseases simultaneously.

"There's nothing like that on a single chip right now," Sohn says. "And the fact that it's electronic and requires so little preparation means that you can imagine someday having everything in a cell phone-type device that can transmit the results of the test to a physician far away."

Lydia Sohn's home page

"Direct detection of antibody-antigen binding using an on-chip artificial pore" by Omar A. Saleh and Lydia L. Sohn (Proceedings of the National Academy of Science, Jaunary 27, 2003)

"Lydia Sohn joins ME faculty in micro-nano engineering"

"Big trouble in the world of big physics" by Leonard Cassuto (Salon, September 16, 2002)

Lab Notes is published online by the Public Affairs Office of the UC Berkeley College of Engineering. The Lab Notes mission is to illuminate groundbreaking research underway today at the College of Engineering that will dramatically change our lives tomorrow.

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© 2004 UC Regents. Updated 10/01/04.